Rosmarinic Acid Mitigates Lipopolysaccharide-Induced Neuroinflammatory Responses through the Inhibition of TLR4 and CD14
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ORIGINAL ARTICLE
Rosmarinic Acid Mitigates Lipopolysaccharide-Induced Neuroinflammatory Responses through the Inhibition of TLR4 and CD14 Expression and NF-κB and NLRP3 Inflammasome Activation Yicong Wei,1,2 Jianxiong Chen,1 Yonghong Hu,1 Wei Lu,1 Xiaoqin Zhang,1 Ruiguo Wang,1 and Kedan Chu1
The excessive activation of microglia plays a key role in the pathogenesis of neurodegenerative diseases. The neuroprotective properties of rosmarinic acid have been reported in a variety of disease models both in vitro and in vivo; however, the mechanism underlying its anti-neuroinflammatory activity has not been clearly elucidated. In the present study, we evaluated the anti-inflammatory effects of rosmarinic acid in conditions of neuroinflammatory injury in vitro and in vivo. The results indicated that rosmarinic acid reduced the expression of CD11b, a marker of microglia and macrophages, in the brain and dramatically inhibited the levels of inflammatory cytokines and mediators, such as TNFα, IL6, IL-1β, COX-2, and iNOS, in a dose-dependent manner both in vitro and in vivo. Consistent with these results, the expression levels of TLR4 and CD14 and the phosphorylation of JNK were also reduced. Further study showed that rosmarinic acid suppresses the activation of the NF-κB pathway and NLRP3 inflammasome, which may contribute to its anti-inflammatory effects. These results suggest that rosmarinic acid significantly reduced TLR4 and CD14 expression and NF-κB and NLRP3 inflammasome activation, which is involved in antineuroinflammation. Abstract—
KEY WORDS: rosmarinic acid; neuroinflammation; microglia; TLR4; CD14; NF-κB; NLRP3.Yicong Wei and Jianxiong Chen contributed equally to this work.
INTRODUCTION
Yicong Wei and Jianxiong Chen contributed equally to this work. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10753-017-0728-9) contains supplementary material, which is available to authorized users. 1
Centre of Biomedical Research & Development, Fujian University of Traditional Chinese Medicine, No. 1 Huatou Road, Minhou Shangjie, Fuzhou, China 2 To whom correspondence should be addressed at Centre of Biomedical Research & Development, Fujian University of Traditional Chinese Medicine, No. 1 Huatou Road, Minhou Shangjie, Fuzhou, China. Email: [email protected]
Microglia are the brain resident macrophage-like population involved in first-line innate immunity in the central nervous system (CNS) [1, 2]. Activated microglia play a key role in pathogenesis in neurodegenerative diseases [2], and excessive microglial activation plays a major pathophysiological role in cerebral ischemia [3, 4]. The activated microglial cells increase the expression of a variety of proinflammatory genes, such as iNOS (inducible nitric oxide synthase), COX-2 (cyclooxygenase-2), TNF-α (tumor necrosis factor-alpha), and IL-1β (interleukin-1 beta) [2]. These proinflammatory mediators and cytokines,
0360-3997/18/0000-0001/0 # 2018 Springer Science+Business Media, LLC, part of Springer Nature
Wei, Chen
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